Cerebrospinal Fluid Marker Concentrations

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The evaluation of cerebrospinal fluid (CSF) for P-hCG can be a valuable tool in the diagnosis of CNS metastases from GCTs. In patients in whom P-hCG is the predominant marker, measurement of CSF P-hCG may detect patients with CNS involvement with metastatic disease that is below the limits of detection by CT.6 The original work undertaken by Bagshawe and colleagues29,30 (in the era prior to CT and MRI) suggested that a high CSF P-hCG level was predictive of CNS disease. The cutoff for prediction of the presence of CNS metastases was where the CSF concentration exceeded 2% of the serum concentration. In confirmation of this finding, investigators at Memorial Sloan-Kettering Cancer Center reported that a CSF concentration greater than 2% of the serum concentration was of positive predictive value for CNS metastases at autopsy or on imaging studies (Table 17-4).4 Similarly, Kaye and colleagues found that a CSF P-

Figure 17-3. Metastatic mixed nonseminomatous germ cell tumor. The patient was a 24-year-old man who presented with testicular pain and abdominal bloating. Examination revealed right testicular induration and an upper abdominal mass on the right side. His abdominal computed tomography (CT) scan (A) demonstrated a large retroperitoneal mass. There were no lung metastases seen on chest CT. The preoperative serum a-fetoprotein (AFP) level was 18,345 ng/mL, the serum beta-human chorionic gonadotropin (p-hCG) level was 302 ng/mL, and the lactate dehydrogenase (LDH) level was 704 U/L. Inguinal orchiectomy was undertaken, and histopathologic study showed a mixed pattern including major elements of embryonal malignant teratoma and seminoma as well as a small element of choriocarcinoma. Postoperative serum AFP was 7,435 ng/mL, serum p-hCG was 76 ng/mL, and the LDH was 673 U/L. The patient then commenced his first cycle of POMB/ACE chemotherapy. Midway through the first cycle of chemotherapy, the patient complained of headache and difficulty with balance. Magnetic resonance imaging scans of the brain (B to E) demonstrated a single right cerebellar metastasis adjacent to the midline.The metastasis was removed at craniotomy (F and G).The histopathologic differential diagnosis of the brain lesion included primitive neuroectodermal tumor . However, it was only when the case was reviewed at a multidisciplinary case conference that it became clear that the brain lesion was a metastasis derived from one of the elements of the retroperitoneal cancer. (The retroperitoneal mass is shown in H; the cerebellar mass is shown in I). Immunohistochemistry for a variety of molecules including myoglobin provided further evidence for common tumor derivation (J, retroperitoneal mass; K, cerebellar mass). Postoperatively, the patient was scheduled for further chemotherapy and radiation therapy. Unfortunately, he failed to attend follow-up appointments. Six weeks after his craniotomy he was taken by his family to the emergency room because of an inability to walk and a decreased level of consciousness. CT scans of the brain (L and M) showed intracerebellar hemorrhage with secondary hydro-cephalus. Despite ventriculo-peritoneal shunting, the patient deteriorated and died several days later.

hCG concentration greater than 2.5% of the serum P- the described cutoff of about 2% are of little value hCG concentration was highly predictive of CNS because they do not exclude the presence of CNS involvement with GCT.6 CSF P-hCG values lower than metastases.4,6 Measurement of CSF a-fetoprotein has

Figure 17-4. Metastatic yolk sac tumor. The patient is a 28-year-old man. In November 1998, he presented to another hospital with a leftside testicular mass 8 cm in diameter. He underwent orchiectomy, but details on histopathology, marker status, and postoperative therapy are not available. In November 2001, he presented to our medical center with cough and shortness of breath. Chest radiography demonstrated multiple pulmonary metastases and a mediastinal mass. A transbronchial biopsy specimen showed an undifferentiated malignancy consistent with yolk sac tumor, as well as elements suggestive of teratoma (A). The serum a-fetoprotein (AFP) concentration was 8,967 ng/mL, the human chorionic gonadotropin level was 7 mIU/mL, and lactate dehydrogenase was 197 U/L. Computed tomography (CT) of the chest, abdomen, and pelvis confirmed the presence of bilateral lung metastases and a mediastinal mass and demonstrated metastases to the liver, spleen, and right adrenal gland (B and C). Magnetic resonance imaging (MRI) of the brain was ordered, but the patient failed to attend on two occasions. Neurologic examination was normal. The decision was made to start the patient on POMB/ACE chemotherapy in January 2002. He tolerated therapy well, and the serum AFP fell to a level of < 100 ng/mL by April 2002. During this time, he failed to attend further appointments for cerebral MRI, and his serum AFP level plateaued at around 20 ng/mL and then rose to 297 ng/mL. He was started on gemcitabine and paclitaxel, and his serum AFP stabilized at around 200. In May 2002, the patient developed the sudden onset of a right-sided frontal headache, vomiting, and blurring of vision and was taken to the emergency room. A cerebral CT scan (D) demonstrated a right frontal mass lesion, 4 cm in diameter, with intralesion hemorrhage, surrounding edema, and midline shift. While undergoing CT, the patient's affect became altered, and his level of consciousness declined. He was administered dexamethasone intravenously and was taken to the operating room. A right frontal craniotomy was performed, and evacuation of intracranial hematoma was undertaken. Given the clinical condition of the patient, excision of the metastasis was not attempted. Histopathologic examination demonstrated 90% yolk sac tumor and 10% teratoma, with elements of glandular epithelium, cartilage, and immature brain as well as surrounding hemorrhage (E and F). The patient recovered well. Postoperative MRI scans (G and H) showed the previously identified frontal lesion and a small adjacent lesion. The patient was planned for radiation therapy with bilateral subtotal brain fields (50 Gy in 25 fractions over 5 weeks) and a 10 Gy boost to the right frontal lobe (/). After radiation therapy, the patient was functionally well, and restaging before consideration of further systemic therapy was planned.

no clinical usefulness.4 The value of routine CSF examination in patients with normal MRI scans has not been prospectively evaluated because most of the data available come from studies that were done prior to the use of MRI and in which CT was infrequently performed. In contemporary practice, many clinicians reserve quantification of CSF P-hCG for patients who have equivocal MRI findings or who have normal scans but garner a high index of suspicion based on serum P-hCG level and/or bulky pulmonary disease.

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